Bacterial biofilms are a complex organization of bacteria anchored to a surface. They begin as a random collection of independent free-floating, planktonic bacteria, which then is attach to a surface and begin to form microcolonies. When bacterial density reaches a critical point, inter-bacterial crosstalk triggers a phenomenon known as “quorum sensing.” Quorum sensing in turn initiates a cascade of protein expression which ultimately leads to the biofilm phenotype. This phenotype is marked by the formation of towers composed of layers of embedded live bacteria with intertwining water channels nourishing the individual bacteria and demonstrates a functional heterogeneous community. The “mortar” for these structures is comprised of a bacterially extruded exopolysaccharide matrix, which makes up as much as 90% of the biofilm. Importantly, the bacterial component of the biofilm can revert back to the mobile/planktonic state either through intrinsic (bacterial genetic program) or extrinsic (sheer stress) forces thereby causing new acute infections in remote sites (FIG. 1).
Existing in the biofilm phenotype, bacteria can evade host defenses and demonstrate massively decreased susceptibility to antibiotic therapy. For example, the minimal biofilm eradication concentration (MBEC) for pseudomonas biofilms has been demonstrated to be 60 fold greater than the MIC (for planktonic pseudomonas) for gentamicin and greater than 1,000 fold for ceftazidime and piperacillin. Thus, in the biomedical context, infections with associated biofilm formation are very problematic because of their increased resistance to antibiotic therapy and chronic cyclical persistence.
The typical clinical scenario of a biofilm associated infection, is clinical resolution of the initial presenting symptoms while the patient is undergoing antibiotic therapy, i.e, the planktonic bacteria are cleared. However, shortly after antibiotic therapy is terminated the patient presents with symptoms identical to the initial presentation since bacteria in the biofilm state survived therapy and reinfected the host with planktonic cells. Typically, the organisms cultured from the ensuing infections are identical in speciazation and sensitivities as the initial infection (demonstrating non plasmid associated resistance). Biofilms have now been implicated in many infectious processes, including dental caries, periodontitis, otitis media, musculoskeletal infections, necrotizing fasciitis, biliary tract infection, osteomyelitis, to bacterial prostatitis, native valve endocarditis, cystic fibrosis pneumonia as well as infections associated with all hardware (artificial joints, valves, shunts etc.). Recent studies have identified biofilms in the sinus mucosa of patients with chronic rhinosinusitis.
Therefore, there is a need for methods and compositions that are capable of inhibiting is the formation and growth of biofilms.